Evolution Of Glomerular Filtration Rate Research Articles

Kidney Measurement and Glomerular Filtration Rate Evolution in Children with Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron, and over time the cystic dilatation leads to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts leads to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and hematuria. However, the presentation of ADPKD varies in children, from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by a mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end-stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra-normal kidney function, we explored the glomerular filtration rates dynamics and the renal ultrasound-adjusted percentiles. In total, 14 out of 16 patients had kidney percentiles over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 ± 33.07 mL/min/1.73 m2, p = 0.14). Also, when the quadratic equation was employed, not even a single patient reached the glomerular hyperfiltration threshold. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1 year of follow-up (quadratic ΔeGFR = -0.32 ± 5.78 mL/min/1.73 m2), as opposed to the Schwartz formula that can falsely classify children in a hyperfiltration state (ΔeGFR = 7.51 ± 19.46 mL/min/1.73 m2), p = 0.019.

Follow-Up of Blood Pressure, Arterial Stiffness, and GFR in Pediatric Kidney Transplant Recipients.

Pediatric renal transplant recipients (RTx) were studied for longitudinal changes in blood pressure (BP), arterial stiffness by pulse wave velocity (PWV), and graft function.Patients and Methods: 52 RTx patients (22 males) were included; office BP (OBP) and 24 h BP monitoring (ABPM) as well as PWV were assessed together with glycemic and lipid parameters and glomerular filtration rate (GFR) at 2.4[1.0–4.7] (T1) and 9.3[6.3–11.8] years (T2) after transplantation (median [range]).Results: Hypertension was present in 67 and 75% of patients at T1 and T2, respectively. Controlled hypertension was documented in 37 and 44% by OBP and 40 and 43% by ABPM. Nocturnal hypertension was present in 35 and 30% at T1 and T2; 24 and 32% of the patients had masked hypertension, while white coat hypertension was present in 16 and 21% at T1 and T2, respectively. Blood pressure by ABPM correlated significantly with GFR and PWV at T2, while PWV also correlated significantly with T2 cholesterol levels. Patients with uncontrolled hypertension by ABPM had a significant decrease in GFR, although not significant with OBP. Anemia and increased HOMAi were present in ~20% of patients at T1 and T2.Conclusion: Pediatric RTx patients harbor risk factors that may affect their cardiovascular health. While we were unable to predict the evolution of renal function based on PWV and ABPM at T1, these risk factors correlated closely with GFR at follow-up suggesting that control of hypertension may have an impact on the evolution of GFR.

Impact of Tacrolimus Daily Dose Limitation in Renal Transplant Recipients Expressing CYP3A5: A Retrospective Study.

The pharmacokinetic variability of tacrolimus can be partly explained by CYP3A5 activity. Our objective was to evaluate a tacrolimus sparing policy on renal graft outcome according to CYP3A5 6986A>G genetic polymorphism. This retrospective study included 1114 recipients with a median follow-up of 6.3 years. Genotyping of the 6986A>G allelic variant corresponding to CYP3A5*3 was systematically performed. One year after transplantation, tacrolimus blood trough concentration (C0) target range was 5–7 ng/mL. However, daily dose was capped to 0.10 mg/kg/day regardless of the CYP3A5 genotype. A total 208 CYP3A5*1/- patients were included. Despite a higher daily dose, CYP3A5*1/- recipients exhibited lower C0 during follow-up (p < 0.01). Multivariate analysis did not show any significant influence of CYP3A5*1/- genotype (HR = 0.70, 0.46–1.07, p = 0.10) on patient-graft survival. Glomerular Filtration Rate (GFR) decline was significantly lower for the CYP3A5*1/- group (p = 0.02). The CYP3A5*1/- genotype did not significantly impact the risk of biopsy-proven acute rejection (BPAR) (HR = 1.01, 0.68–1.49, p = 0.97) despite significantly lower C0. Based on our experience, a strategy of tacrolimus capping is associated with a better GFR evolution in CYP3A5*1/- recipients without any significant increase of BPAR incidence. Our study raised some issues about specific therapeutic tacrolimus C0 targets for CYP3A5*1/- patients and suggests to set up randomized control studies in this specific population.

Analyzing the Impact of Bariatric Surgery in Kidney Function: a 2-Year Observational Study.

Obesity is an independent risk factor for chronic kidney disease (CKD). Our aims were: (1) to evaluate the impact of bariatric surgery (BS) on kidney function, (2) clarify the factors determining postoperative evolution of glomerular filtration rate (ΔGFR) and urinary albumin-to-creatinine ratio (ΔUACR), and (3) access the occurrence of oxalate-mediated renal complications. We investigated a cohort of 1448 obese patients who underwent BS. Those with baseline-estimated GFR (eGFR0) < 30mL/min or without information about the 2-year post-surgical eGFR (eGFR2) were excluded. A total of 725 patients were included. At baseline, 38(5.2%) had hyperfiltration with eGFR0 ≥ 125mL/min/1.73m2 (G0), 492 (67.9%) had eGFR0 90-124mL/min/1.73m2 (G1), 178 (24.6%) had eGFR0 60-89mL/min/1.73m2 (G2), and 17 (2.3%) had eGFR0 < 60mL/min/1.73m2 (G3). ΔGFR significantly increased in 96.6% (ΔGFR = 23.8 (IQR 15.9-29.8)) and 82.4% (ΔGFR = 18.6 (IQR 3.6-44.0)) of the subjects with G2 and G3 CKD, respectively (p < 0.001). The variables independently associated with ΔGFR were baseline body mass index (BMI) (positively), high blood pressure (HBP) (negatively), and fasting plasma glucose (FPG) (negatively), as well as FPG variation (positively). An overall prevalence of high UACR (≥ 30mg/g-1) of 17.9% was found, with 81.5% of these subjects presenting A2(30-300mg/g-1) and 18.5% A3(> 300mg/g-1) UACR. UACR significantly decreased after BS (p < 0.001). Significant predictors of ΔUACR were BMI, systolic blood pressure, and HbA1c. Urinary excretion of calcium oxalate crystals was found in 77(11.1%) patients, with only 1 presenting oxalate-mediated renal complications. ΔGFR seems to be influenced by the initial kidney function, as it decreases in subjects with hyperfiltration but tends to increase in those with kidney dysfunction. These results suggest that BS is associated with improvement of kidney outcomes, without a significant increase in renal complications.

Evolution of blood pressure in children with congenital and acquired solitary functioning kidney

BackgroundIt is not yet clear if blood pressure and renal function changes evolve differently in children with a congenital or acquired solitary functioning kidney. This study aims to assess if there are any differences between these two types of solitary kidney patients.MethodsCurrent research is a retrospective study assessing the evolution of glomerular filtration rate, proteinuria, and blood pressure in clinical records of 55 children with a solitary functioning kidney (37 congenital and 18 acquired). We used the medical records of children who had been assisted, in our unit of pediatric nephrology, for a period of 14 years (168 months), from the time of diagnosis, between January/1997 and December/2015.ResultsDuring the study period, glomerular filtration rate (T0 128.89 ± 32.24 vs T14 118.51 ± 34.45 ml/min/1.73 m2, p NS) and proteinuria (T0 85.14 ± 83.13 vs T14 159.03 ± 234.66 mg/m2/die, p NS) demonstrated no significant change. However, after 14 years of follow-up 76.4% of patients had increased levels of arterial hypertension with values over the 90th percentile for gender, age, and height. Specifically, children with an acquired solitary functioning kidney mainly developed hypertension [T0 2/17 (12%) vs T14 9/17 (52.9%) p < 0.025], whereas children with a congenital solitary functioning kidney mainly developed pre-hypertension [T0 3/38 (7.9%) vs T14 17/38 (44.7%) p < 0.0005].ConclusionsThe renal function of children with solitary functioning kidneys remains stable during a follow-up of 14 years. However, these children should be carefully monitored for their tendency to develop arterial blood pressure greater than the 90th percentile for gender, age, and height.

Renal abnormalities in a cohort of HIV-infected children and adolescents.

This study aimed to identify the prevalence of renal abnormalities and the evolution of glomerular filtration rate (GFR) among human immunodeficiency virus (HIV)- infected children and adolescents followed up in an infectious disease outpatient pediatric clinic. We performed a cohort study of 115 children and adolescents. Outcomes of two evaluations for urinalysis, microalbuminuria/urinary creatinine ratio, urinary retinol-binding protein (uRBP) concentration, and estimated GFR (eGFR) were obtained for each patient, with an average interval of 6 months between evaluations. These changes were correlated with gender, age, race, body mass index (BMI), height-for-age (H/A) percentile, clinical and immunological classification of HIV infection, use of antiretroviral therapy (ART), HIV viral load (VL), and CD4+ T-lymphocyte count. Mean patient age at the time of inclusion in the study was 12.6 ± 3.2years; 50.4% were male, 81.7% had acquired immune defeciency syndrome (AIDS), 80.9% had CD4+ < 500 cells/mm(3), and 87.8% were on ART. Urinary changes included hematuria (11.3%), proteinuria (7%), and microalbuminuria (11.6%); uRBP was present in 3.8%; and mean eGFR was 163 ± 32ml/min/1.73m(2). The subclinical renal abnormalities found in this study may indicate early manifestations of a broad spectrum of renal dysfunction associated with HIV and involves the decision to initiate or modify ART.

Evolution of glomerular filtration rate in patients with essential hypertension: impact of type 2 diabetes

groups. In addition, night time BP medication dose was increased with the objective to achieve 10% nocturnal drop in SBP in those randomized to the chronotherapy arm. iGFR was repeated at 12 months. Results are presented in a tabular format. Conclusions: In kidney transplant recipients without OSA and with acceptable kidney function and abnormal circadian BP pattern at 1 month from tx only a minority will achieve normal day-night BP pattern at 1 year from tx despite nocturnal dosing of BP medications.

Evolution of glomerular filtration rate in HIV‐infected, HIV–HBV‐coinfected and HBV‐infected patients receiving tenofovir disoproxil fumarate

We aimed to compare the evolution of estimated glomerular filtration rate (eGFR) in HIV-, HIV-HBV- and HBV-infected patients treated with tenofovir disoproxil fumarate (TDF). Three groups of patients receiving TDF > 12 months were recruited: 194 HIV-infected patients, 85 HIV-HBV-coinfected patients and 50 HBV-infected patients. eGFR was estimated using the Modification of the Diet in Renal Disease (MDRD) equation. Multivariate regression models were constructed to estimate factors associated with eGFR decrease from baseline. A total of 329 patients were studied. Median follow-up was 2.7 years. Median eGFR decrease was -4.9 (-16.6 to +7.2) mL/min/1.73 m(2) . After multivariate stepwise regression analysis, age (P = 0.0002), non-African origin (P < 0.0001), baseline eGFR (P < 0.0001) and TDF duration (P = 0.02) were associated with eGFR decrease in the whole population, while hypertension, diabetes and type of infection were not. Age (P < 0.0001), non-African origin (P = 0.0004), baseline eGFR (P < 0.0001) and TDF duration (P = 0.007) remained associated with eGFR decline in HIV and HIV-HBV-infected patients, while other variables including HIV risk factor, CDC stage, CD4 and HIV-RNA levels were not. Age (P = 0.03), non-African origin (P = 0.004), baseline eGFR (P < 0.0001) and baseline HBV-DNA > 2000 IU/mL (P = 0.04) were associated with eGFR decline in HBV and HIV-HBV-infected patients, while other variables including HBV risk factor and fibrosis stage were not. Estimated glomerular filtration rate decline under TDF therapy appears mainly associated with older age, non-African origin, higher baseline eGFR and longer TDF administration but not with the type of viral infection. Regular follow-up of renal function, especially tubular function is recommended during TDF therapy.

Impact of emtricitabine/tenofovir (FTC/TDF) on renal function in antiretroviral‐naïve patients≥50 years ‐ TRIP study

PurposeIn the last decade the prevalence of HIV‐infected patients≥50 years of age has increased. FTC/TDF is nowadays one of the cornerstones of cART in naïve patients, generally considered safe and well tolerated; nevertheless there is a continuous debate about the renal safety of TDF, due to the report of cases linking this treatment with renal failure and tubular dysfunction. In addition, there is a well‐recognized age‐related decline in renal function. Our aim was to describe the impact of cART regimen (FTC/TDF vs. others) on renal function of subjects who start cART at≥50 years old.MethodsNational, retrospective cohort analysis of HIV‐infected patients&gt;50 y at the time they began the first cART (Jan 1, 2006 – Dec 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF versus other NRTI regimens (no TDF). For this analysis we excluded subjects taking potentially nephrotoxic drugs at baseline. We compared the impact of FTC/TDF vs. no‐TDF regimens (main groups) on renal function by means of the changes, during the first 12 months of treatment, in glomerular filtration rate estimated by the CKD‐EPI formula, and by the analysis of time to renal deterioration during the complete follow up (defined as progression to an EPI‐CKD value&lt;60 mL/min/1.73 m2 in subjects with baseline values&gt;60). We also compared these outcomes among FTC/TDF users, according to the third agent: PI vs. NNRTI, and lopinavir/r vs. efavirenz.ResultsWe included 125 patients, median age: 54.8 y, 82% males, median CD4 count 235 cells/µl, median viral load 4.7 log, follow up: median 19 months, max: 66 months. Of them, 82 started with FTC/TDF and 43 with other NRTIs (no TDF). During the follow‐up 13/125 patients taking FTC/TDF (11%) presented with renal deterioration. The Cox regression model including age, sex, transmission category, baseline CD4 count and viral load, FTC/TDF use, PI/NNRTI use, and LPVr/EFV use showed a hazard ratio for renal deterioration of 4.13 (95% CI 0.92, 18.5) for LPV/r users. The table shows the evolution of glomerular filtration rate, and proportion and risk of renal deterioration.ConclusionIn subjects starting cART after 50 years of age, we have not found significant changes in glomerular filtration rate associated with the use of FTC/TDF‐based regimens. Overall, the risk of renal deterioration was 4.1 times higher for LPV/r users (almost statistically significant). Among FTC/TDF users, this risk was 8 times higher for LPV/r as compared to EFV. Overall Among TDF users No TDF vs. TDF/FTC PI vs. NNRTI LPV vs. EFV Glomerular filtration rate by CKD‐EPI (mL/min/1.73 m2) Baseline (median)* 91.6 vs. 93.7 90.7 vs. 95.7 93.7 vs. 95.8 Month 12 (median)* 98.0 vs. 95.1 89.2 vs. 96.7 71.2 vs. 97.8 (p &lt; 0.05) Renal deterioration: Cases (n, %) 4/38 (10.5%) vs. 9/79 (11.4%) 5/33 (15.1) vs. 4/45 (8.9) 4/21 (19.0) vs. 3/40 (7.5) Log rank (time to event) 0.883 0.278 0.055 Crude HR (95% CI) 1.09 (0.34, 3.55) 2.06 (0.54, 7.86) 3.96 (0.87, 17.93) Adjusted HR** (95% CI) 0.60 (0.15, 2.35) 3.37 (0.76, 14.87) 8.20 (1.30, 51.75) All comparisons between arms, and between baseline and month 24 were not statistically significant unless otherwise indicated. Adjusted by age, sex, transmission category and baseline CD4 count and viral load.

Evolution of renal function in patients treated with antiangiogenics after nephrectomy for renal cell carcinoma

Purpose Side effects of antiangiogenic agents are moderate compared with other therapies. The most frequent adverse events are of a renovascular origin and manifest as hypertension (HTN) and thrombotic microangiopathy. To date, data are scanty on the renal tolerance of such drugs regarding renal function as itself, i.e., glomerular filtration rate (GFR). We report on the evolution of GFR in patients receiving antiangiogenic therapy after unilateral nephrectomy for kidney cancer. Patients and methods Data from 73 patients followed in our oncology department for kidney cancer, who had undergone unilateral nephrectomy, and received any antiangiogenic therapy were reviewed. Their GFR was calculated using the aMDRD formula. Results All patients showed a declining renal function over time (−1.23 and −2.51 mL/min/1.73 m 2 using the slope of the curve or the difference between GFR at baseline and that at the end of treatment, respectively). Among them, patients who were recorded as having HTN before initiation of antiangiogenic therapy showed a higher decrease in their GFR of −13.28 and −12.06 mL/min/1.73 m 2. Conclusion We recommend that blood pressure should be measured closely in those patients before initiation of antiangiogenic therapy. When HTN is diagnosed, it should be treated and renal function should be monitored since those patients may be at risk for rapidly decreasing renal function under therapy.

Importance of glycemic control on the course of glomerular filtration rate in type 2 diabetes with hypertension and microalbuminuria under tight blood pressure control

Background and aims To evaluate the role of glycemic control on the evolution of glomerular filtration rate (GFR) in type 2 diabetes (T2DM) with mild-moderate hypertension under tight blood pressure control, and to address the current controversy whether diabetic nephropathy worsens, independently of blood pressure, proportionally to HbA1c at any physiological level or only when HbA1c is above a 7.5–8% threshold. Methods and results T2DM ( N = 127) during early stage diabetic nephropathy characterized by microalbuminuria were followed during a 2 year multicenter study. Individual GFR profiles were accurately obtained by 51Cr – EDTA bolus injections and analyzed with linear statistical mixed-effects models. GFR at baseline was significantly negatively correlated with age and plasma creatinine concentration ( P ≤ 0.0001), and GFR declined, on average, by 4.0 ml/min 1.73 m 2/year ( P = 0.001). A significant correlation was found between individual GFR decline rate and average systolic (SBP) and diastolic (DBP) blood pressures (−0.254 (0.736) ml/min 1.73 m 2/year per mmHg increase in SBP (DBP), P = 0.041 (0.014)) and % of glycated hemoglobin (HbA1c) (−1.78 ml/min 1.73 m 2/year per % increase in HbA1c, P = 0.048). This implies a 44% increase/reduction in GFR decline rate for 1% HbA1c increase/reduction around 7.0% (i.e. 5.79 and 2.24 ml/min 1.73 m 2/year at 8% and 6% HbA1c, respectively). Conclusions This study demonstrates that, despite tight blood pressure control, an accurate glycemic control till very low patterns of HbA1c (from 10–11% to 5–6%) is needed to delay the progression of GFR decay in Mediterranean T2DM in south Europe with microalbuminuria.

Glomerular filtration rate changes in normoalbuminuric and microalbuminuric Type 2 diabetic patients and normal individuals: A 10-year follow-up

Aim To analyze the changes in the glomerular filtration rate (GFR) in a cohort of normoalbuminuric Type 2 diabetic (DM 2) patients and nondiabetic individuals. Methods Sixty-five normoalbuminuric DM 2 patients [urinary albumin excretion rate (UAER) <20 μg/min] and 44 nondiabetic individuals recruited at baseline were followed for a mean period of 10±1 years. In addition to conventional clinical and metabolic variables, GFR ( 51Cr-EDTA technique) and UAER (immunoturbidimetric method) measurements were performed at baseline and at follow-up. We also evaluated the presence of diabetic retinopathy, hypertension, and cardiovascular disease. Multiple linear regression was performed to assess variables independently associated with GFR evolution in patients with Type 2 diabetes. Results Fifty DM 2 patients and 32 nondiabetic individuals were included in the follow-up evaluation. Fourteen out of the 50 patients with Type 2 diabetes developed microalbuminuria. They presented a faster GFR decline (−0.39±0.24 ml/min/month; ANOVA, P=.0013) than did persistently normoalbuminuric (−0.16±0.16 ml/min/month) and nondiabetic individuals (−0.13±0.14 ml/min/month). Multiple linear regression analysis disclosed baseline fasting plasma glucose (FPG) along with the development of microalbuminuria as factors significantly related to a higher GFR decline. Conclusions Persistently normoalbuminuric patients and normal individuals presented a similar degree of GFR reduction related to the aging process. The slope was significantly enhanced in patients who developed microalbuminuria and was influenced by worse baseline glucose control.

Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction.

Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction. We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year. We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF. This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.

Five-Year Prospective Study of Glomerular Filtration Rate and Albumin Excretion Rate in Normofiltering and Hyperfiltering Normoalbuminuric NIDDM Patients

To evaluate the evolution of glomerular filtration rate (GFR) and albumin excretion rate (AER) of normofiltering (NF) and hyperfiltering (HF) normoalbuminuric NIDDM patients. A longitudinal study of 32 normoalbuminuric (AER < 20 micrograms/min) NIDDM patients and 20 age-, sex-, and BMI-matched normal individuals was done. Subjects had their GFR (51Cr-labeled EDTA single-injection method) measured at entry and after 40 and 60 months. At entry, 13 NIDDM patients had GFR values above the upper limit of the normal range in our laboratory (> 137 ml.min-1 x 1.73 m-2) and were considered as HF. In NIDDM patients, the 24-h AER (radioimmunoassay), HbA1c, urinary urea, and mean arterial blood pressure (MBP) were analyzed at entry and after 40 and 60 months. There was a significant decline of GFR in NIDDM patients and normal subjects at 60 months. The decline was significantly greater in HF patients (-0.61 ml.min-1.month-1; P = 0.001) than in NF (-0, 18) and control subjects (-0, 14); the rate of change in NF and control subjects was the same (P > 0.05). In stepwise multiple regression analysis, with GFR decline as the dependent variable and GFR and AER at baseline, age and change in MBP, change in urinary urea, change in HbA1c, and change in therapy as independent variables, only baseline GFR (R2 = 0.19, P = 0.002) and age (R2 = 0.31, P = 0.048) were significantly related to the outcome. At 60 months, AER raised > 20 micrograms/min in three HF and in four NF patients. In logistic regression analysis, only higher initial AER (although still in the normal range; P = 0.037) and an increase in urinary urea (P = 0.021) were significantly related to the later development of microalbuminuria. The GFR of normoalbuminuric NIDDM patients declines significantly over 60 months. This decline is associated to baseline GFR and age. HF NIDDM patients show a faster decline in GFR than NF patients, whose GFR falls at a rate that is compatible with the age-related change observed in normal control subjects. The development of microalbuminuria is related to higher baseline AER and to increases in urinary urea and is similar in NF (4 of 19) and HF (3 of 13) NIDDM patients (P > 0.05).

Importance of donor/recipient body weight ratio as a cause of kidney graft loss in the short to medium term.

The importance of the donor/recipient body weight ratio (DRBWR) as a cause of kidney graft loss was evaluated in 112 non-diabetic, ciclosporin-treated, first cadaver kidney transplant recipients. According to the DRBWR, the patients were divided into three groups: 'low' (< or = 0.80), 'medium' (0.81-1.20), and 'high' (> 1.20). The three groups did not differ in patient or graft survival, and the DRBWR was not a predictor of graft failure at multivariate analysis (Cox models), even after only patients with graft survivals > 1 year were considered. The three groups did not differ in glomerular filtration rate (GFR) and proteinuria 6-60 months after renal transplantation. When the 55 patients with a follow-up period > 4 years were considered, no differences between groups were found in GFR or GFR evolution over time. Hypertension was significantly less frequent in group 'high' (Mantel-Cox p = 0.04), but very likely as a consequence of uneven recipient gender (an independent predictor of hypertension at multivariate analysis) distribution between groups, the significance being lost when survival curves were rebuilt by stratifying for recipient gender. DRBWR never resulted as a significant predictor of GFR at multivariate analysis when GFR values 6-60 months after transplantation were analyzed. We conclude that the DRBWR has no major effects on kidney graft function and survival in the short to medium term.

Evolution of Glomerular Filtration Rate in Proteinuric NIDDM Patients

To evaluate, by means of a precise method, the rate of decline of glomerular filtration rate in proteinuric non-insulin-dependent diabetic (NIDDM) patients. The study was comprised of seven NIDDM patients who visited an outpatient clinic and had a 24-h urinary protein excretion rate greater than or equal to 500 mg in the absence of heart failure, urinary tract infection, or other nephropathies. Glomerular filtration rate (51Cr-labeled EDTA, single-injection protocol) and 24-h proteinuria (turbidimetric method) were assessed at periodic intervals (2-6 mo). Correlation of the measurements with time (Pearson's r, with Student's t test used to assess the significance, alpha = 0.05) was used to evaluate the trend of evolution of glomerular filtration rate. Renal biopsies were performed in four patients. In three of four patients, renal histopathology was consistent with the diagnosis of diabetic nephropathy (in the 4th patient measurements were not satisfactory). Neither glomerular filtration rate nor proteinuria correlated significantly with time, except in one patient who had multiple myeloma. The decline of glomerular filtration rate in proteinuric NIDDM patients is different from that observed in insulin-dependent diabetic patients, which is probably much slower.

Maturational changes in the fetal glomerular filtration rate

Few data are available documenting the evolution of glomerular filtration rate (GFR) during gestation. In order to investigate this aspect, 33 fetal sheep have been studied, with the use of an intrauterine fetal preparation. It appears that the actual GFR (AGFR) in milliliters per minute increased during the last third of gestation without a significant increase in CFR expressed as milliliters per minute per kilogram of fetal weight (GFR-FW) and as milliliters per minute per gram of kidney weight (GFR-KW). It is suggested that a parallel and constant increase in AGFR and in total fetal weight or kidney weight might explain the absence of variation in GFR-FW or GFR-KW during the last third of gestation.

INCREASE IN TOTAL GLOMERULAR FILTRATION RATE DURING GESTATION

To date there have been no studies documenting the evolution of glomerular filtration rate (GFR) during fetal life.In order to investigate this aspect, 33 fetal sheep ranging from 0.4 to 4.2 kg (80-143 days of gestation) have been studied, utilizing an intra-uterine fetal preparation. There was a significant correlation between the increase of actual GFR ml/man (AGFR) and the age of gestation (p≤ 0.05) or the weight of the fetus (p≤ 0.01) or the weight of the kidney (p≤ 0.01). However, there was no significant change when GFR ml/min/kg of total fetal weight (GFR-FW) or GFR ml/min/gm of fetal kidney (GFR-KW) was compared to the age of gestation or the weight of the fetus or the weight of the kidney.It thus appears that the AGFR increases during the last third of gestation without any significant increase in GFR whether expressed as ml/min/kg of fetal weight or ml/min/gm of kidney. The authors suggested that a parallel and constant increase in AGFR and in total fetal weight or kidney weight might explain the absence of variation in GFR-FW or GFR-KW during the last third of gestation.